The cerebral dopaminergic nervous system is involved in several common neurological disorders, including schizophrenia and Parkinson's disease. Radiopharmaceuticals labeled with 18F(beta+, t 1/2=110min) for positron emission tomography (PET) or 123I (159 keV gamma, t 1/2 = 13.2 h) for single photon emission computerized tomography (SPECT) potentially allow noninvasive assessment of cerebral dopaminergic physiology in health and disease. New high-specific activity 18F- and 123I-labeled analogues of the D-2 ligand raclopride, the D-1 ligand SCH-23390, and the presynaptic dopamine transport antagonist GBR-12935 will be synthesized for radiopharmaceutical evaluation. Following preliminary screening using in vitro binding assays and in vivo biodistribution experiments in rats, promising 18F- and 123I-labeled ligands will be studied noninvasively in baboons. The blood-brain-barrier's permeability-surface area product will be measured using residue detection, and the in vivo localization in receptor-rich areas of the brain will be imaged with PET and SPECT. An explicit dynamic model will be applied to the PET data from 18F-labeled ligands to derive rate constants for in vivo receptor binding. The interrelationships of D-2, d-1 and dopamine uptake sites will be examined in PET and SPECT experiments with an MPTP-induced hemiparkinsonized baboon. The utility of SPECT as a clinical receptor-based imaging modality will be assessed by comparing SPECT data for 123I-labeled ligands with PET results for the corresponding 18F-labeled ligands.